Risultati per: Scoperta una nuova molecola anti-cancro

Background
Inflammation is indicated as one of the factors that play a role in the development of schizophrenia, with several studies having found considerable inconsistencies in their results. Few have investigated the role of inflammation in primary psychosis in blood and cerebrospinal fluids simultaneously, the aim of this study being to investigate the expression of blood and cerebrospinal fluid inflammatory cytokines in treatment-naive first-episode psychotic participants.

Methods and analysis
This is a combined cross-sectional and prospective observational study, which is currently taking place in Durban, South Africa, will recruit 60 participants (30 cases and 30 matched controls). The primary objective is to describe baseline CSF and longitudinal expression/levels of inflammatory cytokines in the blood in persons diagnosed with first-episode psychosis (FEP) for 12 months. The secondary objective is to describe the associations between inflammatory cytokines and psychosis severity, neurocognitive performance, antipsychotic response and metabolic changes at different time points (baseline, 3, 6 and 12 months).

Interventions
We will collect the sociodemographic details of all participants, and the Positive and Negative Symptoms Scale, Patient Health Questionnaire-9, Childhood Trauma Scale, Repeatable Battery for the Assessment of Neuropsychological Status Update, metabolic markers and inflammatory markers (venous blood and lumbar puncture cerebrospinal fluid) for those with FEP. Data from matched controls will only be collected at one point and no follow-ups (cross-sectional).

Ethics and dissemination
The study protocol has been approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00004714/2022). The study is nested in an ongoing study titled the burden of HIV and Psychosis in an African setting: a longitudinal study of HIV-infected and non-infected patients with First-Episode Psychosis (BREC 571/18). The results will be actively disseminated through peer-reviewed journal publications and conference presentations.

A Rivoli e Pinerolo, nel Torinese, le prime tre operazioni

Trattamento rapido e tollerato con ridotto impatto estetico

Trattamento rapido e tollerato con ridotto impatto estetico

All’Irccs Negrar per la radioterapia, tecnologia unica in Italia

Studio, una bevanda al giorno aumenta il rischio di 5 volte

Studio, una bevanda al giorno aumenta il rischio di 5 volte

TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease (IBD) is supported by several converging lines of evidence. Herein, we aim to provide a comprehensive understanding of what is currently known regarding the TL1A/DR3 system in the context of IBD. TL1A and DR3 are expressed by cellular subsets with important roles for the initiation and maintenance of intestinal inflammation, serving as potent universal costimulators of effector immune responses, indicating their participation in the pathogenesis of IBD. Recent evidence also supports a homoeostatic role for TL1A:DR3 via regulation of Tregs and innate lymphoid cells. TL1A and DR3 are also expressed by stromal cells and may contribute to inflammation-induced or inflammation-independent intestinal fibrogenesis. Finally, discovery of genetic polymorphisms with functional consequences may allow for patient stratification, including differential responses to TL1A-targeted therapeutics. In conclusion, TL1A:DR3 signalling plays a central and multifaceted role in the immunological pathways that underlie intestinal inflammation, such as that observed in IBD. Such evidence provides the foundation for developing pharmaceutical approaches targeting this ligand-receptor pair in IBD.

Objectives
To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).

Methods
ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA aged ≥18 years who completed a qualifying contRAst trial (contRAst 1–3) and who the investigator thought might benefit from long-term otilimab treatment were eligible to enter contRAst X. Patients who received otilimab (90 mg/150 mg) in their qualifying trial maintained the same dose; patients who received tofacitinib or sarilumab were rerandomised 1:1 to either otilimab dose. Patients could continue background conventional synthetic disease-modifying antirheumatic drugs. The primary objective was long-term safety (up to 4 years).

Results
Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination. For otilimab 90 mg and 150 mg, the incidence of adverse events (AEs) was 62% (n=902/1456) and 64% (n=931/1459), the incidence of AEs of special interest was 8% (n=120/1456) and 7% (n=95/1459) and the incidence of serious AEs was 8% (n=123/1456) and 8% (n=114/1459), respectively. There were no instances of pulmonary alveolar proteinosis (PAP), active tuberculosis (TB), TB reactivation or serious hypersensitivity reactions. The proportions of clinical disease activity index low disease activity responders remained relatively stable throughout, with no apparent reduction following the switch from tofacitinib/sarilumab to otilimab.

Conclusion
No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab.

Trial registration number
ClinicalTrials.gov: NCT04333147.

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